1. Field of the Invention
This invention relates to a process for preparing 4-acetoxyazetidinones of the following formula (I): ##STR3## wherein Z is a hydrogen atom, a lower alkyl group or a hydroxyethyl group which may or may not be protected, which are useful as an intermediate for synthesizing penem antibiotics.
2. Description of the Background Art
Penem antibiotics such as thienamycin have recently been attracting attention as pharmaceuticals because of their wide range antibacterial spectrum.
Several processes of preparing them have already been proposed by Kametani [Heterocycles, 17, 463-506 (1982)] and by Shibuya [Journal of Organic Synthetic Chemistry, 41, 62 (1983)]. Among them, the process via 4-acetoxyazetidinones of formula (I) above is considered advantageous because different penem antibiotics are obtainable owing that the formula (I) compounds are capable of reacting with various nucleophilic agents.
Conventionally known processes for preparing 4-acetoxyazetidinones of formula (I) include a process where 4-hydroxycarbonylazetidinones are oxidized by lead tetraacetate [Tetrahedron Letters, 23, 2293 (1982)], a process where 4-hydroxycarbonylazetidinones are subjected to electrode oxidation [ibid., 29, 1409 (1988)], a process where 4-acetylazetidinones are oxidized by metachloroperbenzoic acid (Japanese Patent Application Laid-Open (Kokai) No. 50964/1986) and a process where 4-silyloxyazetidinone derivatives are reacted with acetic anhydride (European Patent No. 247,378).
In order to introduce an acetoxy group to the 4-position of azetidinones, these processes require first the formation of azetidinones having a specified substituent at the 4-position, then the introduction of an acetoxy group to the 4-position. This is accompanied by some drawbacks, in that the preparation of the azetidinones having a specified substituent at the 4-position is cumbersome, and furthermore, conversion of the substituent at the 4-position into a acetoxy group is difficult. Accordingly, these conventional processes are not beneficial to industrial manufacturing.
Under these circumstances, the present inventors conducted extensive studies and found that a reaction with acetic acid and an oxidizing agent in the presence of a ruthenium catalyst was capable of readily introducing an acetoxy group to the 4-position of azetidinones. This invention was achieved based on this finding.